Ignite Creation Date:
2024-05-06 @ 10:42 AM
Last Modification Date:
2024-10-26 @ 12:33 PM
Study NCT ID:
NCT03321123
Status:
UNKNOWN
Last Update Posted:
2017-10-25
First Post:
2017-09-20
Brief Title:
MB-CART191 in Patients With RR ALL
Sponsor:
Shanghai Childrens Medical Center
Organization:
Shanghai Childrens Medical Center
Study Overview
Official Title:
Adoptive Therapy With MB-CART191 in Patients With RelapsedRefractory CD19-positive B Cell Acute Lymphoblastic Leukemia
Status:
UNKNOWN
Status Verified Date:
2017-10
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Precursor-B acute lymphoblastic leukemia ALL is the most common cancer in childhood Despite major advances in ALL therapy 20 of children and 40-50 of adults fail state-of-the art first-line treatment But there is a strong need for alternative treatments to cure chemotherapy-refractory and relapsed B cell malignancies in pediatric patients Relapsed and refractory B cell malignancies remain a therapeutic challenge as these diseases are characterized by adverse survival These cancers share a cell origin from the B-cell lineage and consequent surface expression of B-lineage markers such as CD19 and CD22 Chimeric antigen receptor CAR engineered T cell therapy has recently emerged as a new modality to target B cell malignancies CARs couple a single-chain Fv scFv domain directed against a B-lineage-specific antigen to T-cell activating intracellular signaling domains CAR gene-modified T cell interaction with target cells occurs in a HLA-independent fashion so that a single vector can be used to treat all patients with cancers that express the target antigen Miltenyi Biotec has established a semi-automated manufacturing process that can be made available to academic settings for systematic exploration of CAR strategies in advanced clinical studies Closed-system operation improved robustness simplified work flows and reduced labor intensity while maintaining strict adherence to regulatory guidelines allows for decentralized manufacturing In the proposed phase II study the investigator will explore autologous 2nd generation CD19 CAR T cell products in patients with relapsed and refractory disease incurable with standard therapies
Detailed Description:
This is an open-label non-randomized phase II paediatric study In this study eligible patients will receive autologous T cells transduced with the lentiviral vector pLTG1563 MB-CART191 at a doesage of 2x10e6 2x10e7 CAR-transduced T cellskg
Upon enrollment leukapheresis will be performed for MB-CART191 generation Patients with high disease burden at screening eg ALL with M3 marrow and 10000L blasts in peripheral blood may receive bridging chemotherapy after leukapheresis to avoid critical tumor lysis syndrome and cytokine release syndrome CRS by subsequent lymphodepleting chemotherapy and CAR transfer
All patients will receive lymphodepleting chemotherapy with fludarabine 30 mgm2d intravenously iv on days -5-4-3 and -2 cyclophosphamide 500 mgm2d iv on day -3-2 before CAR T cell transfer to enhance the in vivo expansion of CAR T cells
Patients will receive freshly prepared MB-CART191 on day 0 corresponding to day 12 48 hours of manufacturing at a dose of 2x10e6 2x10e7kg MB-CART191 T cells as defined in the study design section The appropriate volume for the target cell dose will be drawn up and given as an IV injection over 30 minutes through a large vein peripherally or centrally
The primary objectives are
To assess the safety and tolerability of MB-CART191
To evaluate the biological activity of adoptive transfer of autologous MB-CART191 in patients with RR CD19-positive B cell lymphoblastic leukemia
The primary endpoint is Overall response rate ORRORR in ALL patients is defined as the rate of complete remission CR CRh on day 28
Upon enrollment leukapheresis will be performed for MB-CART191 generation Patients with high disease burden at screening eg ALL with M3 marrow and 10000L blasts in peripheral blood may receive bridging chemotherapy after leukapheresis to avoid critical tumor lysis syndrome and cytokine release syndrome CRS by subsequent lymphodepleting chemotherapy and CAR transfer
All patients will receive lymphodepleting chemotherapy with fludarabine 30 mgm2d intravenously iv on days -5-4-3 and -2 cyclophosphamide 500 mgm2d iv on day -3-2 before CAR T cell transfer to enhance the in vivo expansion of CAR T cells
Patients will receive freshly prepared MB-CART191 on day 0 corresponding to day 12 48 hours of manufacturing at a dose of 2x10e6 2x10e7kg MB-CART191 T cells as defined in the study design section The appropriate volume for the target cell dose will be drawn up and given as an IV injection over 30 minutes through a large vein peripherally or centrally
The primary objectives are
To assess the safety and tolerability of MB-CART191
To evaluate the biological activity of adoptive transfer of autologous MB-CART191 in patients with RR CD19-positive B cell lymphoblastic leukemia
The primary endpoint is Overall response rate ORRORR in ALL patients is defined as the rate of complete remission CR CRh on day 28
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None